1. Field of the Invention:
The present invention relates to novel carboxystyrene derivatives and to leukotriene antagonists and phospholipase inhibitors containing said derivatives as effective ingredients. Description of the Prior Art:
There have been two methods for prophylactically or therapeutically treating allergic diseases.
One inhibits the release of substances mediating anaphylaxis. Representative drugs used for this purpose include disodium cromoglycate: The Merck Index, 9th Edition, 2585 (1976); and tranilast: Nippon Yakuri Gakkai-shi (Bulletin of Japanese Pharmacological Society), 74, 699 (1978).
The second method is to cause antagonists to act against the mediating substances released. Among drugs used in this method, e.g., diphenhydramine, chlorpheniramine, astemizole, terfenadine, clemastine, etc., which antagonize against histamine, one of substances mediating allergic reactions, have been well known.
It was suggested that certain substances which are not antagonized by antihistamic agents and are called slow reacting substances (SRS's) are released from the lung of patients of bronchial asthma: Prog. Allergy, 6, 539 (1962). "SRS" has recently been used as a general term for leukotriene C.sub.4 (LTC.sub.4), leukotriene D.sub.4 (LTD.sub.4) and leukotriene E.sub.4 (LTE.sub.4) Proc. Natl. Acad. Sci. U.S.A., 76, 4275 (1979); ibid., 77, 2014 (1980); and Nature, 285, 104 (1980). SRS has now been considered to be an important factor involved in human asthmatic ictus: Proc. Natl. Acad. Sci. U.S.A., 80, 1712 (1983).
Some leukotriene antagonists have been known from patent or other publications. For example, FPL-55712 represented by the following formula: ##STR1## is disclosed in Agents and Actions, 9, 133 (1979); KC-404 represented by the following formula: ##STR2## is disclosed in Jap. J. Pharm., 33, 267 (1983); ONO-1078 represented by the following formula: ##STR3## is disclosed in Yuki Gosei Kagaku (Organic Synthetic Chemistry), 45(2), 136 (1987); and LY-171883 represented by the following formula: ##STR4## is also disclosed in J. pharmacol. Exp. Ther., 233(1), 148 (1985).
However, no practical use of such antagonists has been reported.
Certain compound which resemble the compounds according to the present invention in chemical structure have also known. For example, the compound represented by the following formula: ##STR5## is described in German Pat. Publication (Offenlegungsschrift) No. 2,331,444; and the compound represented by the following formula: ##STR6## is also described in J. Prakt. Chem., 6, 72 (1958). However, the leukotriene antagonizing activity of such compounds is not disclosed therein.